A selective cyclin-dependent kinase 4, 6 dual inhibitor, Ribociclib (LEE011) inhibits cell proliferation and induces apoptosis in aggressive thyroid cancer

Lee, Hyun Joo,Lee, Woo Kyung,Kang, Chan Woo,Ku, Cheol Ryong,Cho, Yoon Hee,Lee, Eun Jig Elsevier 2018 Cancer letters Vol.417 No.-

<P><B>Abstract</B></P> <P>The RB-E2F1 pathway is an important mechanism of cell-cycle control, and deregulation of this pathway is one of the key factors contributing to tumorigenesis. Cyclin-dependent kinases (CDKs) and Cyclin D have been known to increase in aggressive thyroid cancer. However, there has been no study to investigate effects of a selective CDK 4/6 inhibitor, Ribociclib (LEE011), in thyroid cancer. Performing Western blotting, we found that RB phosphorylation and the expression of Cyclin D are significantly higher in papillary thyroid cancer (PTC) cell lines as well as anaplastic thyroid cancer (ATC) cell lines, compared with normal thyroid cell line and follicular thyroid cancer cell line. LEE011 dose-dependently inhibited RB phosphorylation and also decreased the expressions of its target genes such as <I>FOXM1, Cyclin A1,</I> and <I>Myc</I> in ATC. Furthermore, LEE011 induced cell cycle arrest in G0-G1 phase and cell apoptosis, and inhibited cell proliferation in ATC. Consistently, oral administration of LEE011 to ATC xenograft models strongly inhibited tumor growth with decreased expressions of pRB, pAKT and Ki-67, and also significantly increased tumor cell apoptosis. Taken together, our data support the rationale for clinical development of the CDK4/6 inhibitor as a therapy for patients with aggressive thyroid cancer.</P> <P><B>Highlights</B></P> <P> <UL> <LI> pRB and Cyclin D were expressed high in aggressive thyroid cancer. </LI> <LI> LEE011 suppressed pRB and also decreased the expressions of its target genes in ATC. </LI> <LI> LEE011 induced cell cycle G1 arrest and apoptosis, and inhibited cell proliferation. </LI> <LI> LEE011 inhibited in vivo tumor growth with decreased expressions of pRB and Ki-67. </LI> <LI> We could explain the anticancer effects with the RB-E2F pathway. </LI> </UL> </P>

골수이식 후 골밀도 및 골대사의 변화 : 2년 추적관찰 2-Year Prospective Study

이원영,강무일,오은숙,오기원,한제호,손현식,윤건호,차봉연,이광우,손호영,강성구,신완식,민우성,김춘추 대한내분비학회 2000 Endocrinology and metabolism Vol.15 No.4·5

동종골수이식 후 혈당 및 혈중 지질농도의 변화양상 및 관련인자

이원영,강무일,오은숙,오기원,손현식,윤건호,차봉연,이광우,손호영,강성구,신완식,민우성,김춘주 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.24 No.6

연구배경:골수이식은 비교적 젊은 연령의 환자들을 대상으로 하며 면역억제제의 사용기간이 비교적 짧으므로, 주로 고령의 만성 질환 환자에서 시행되는 고형장기이식에서와는 달리 당대사 및 지단백 대사에 있어서 많은 차이점이 있을 것으로 추측된다. 저자들은 전향적 연구를 통하여 골수이식 후 시기별로 혈당 및 혈중지단백 변화 양상을 알아보고 이와 관련된 임상인자들을 규명하고자 하였다. 방법:1998년 10월부터 1999년 8월까지 가톨릭대학교 성모병원에서 동종골수이식을 시행한 환자들 중 43명을 대상으로 이식 전 및 이식 후 1, 2, 3, 4주와 3개월, 6개월에 공복 혈당, 혈중 총 콜레스테롤, 중성지방, 고밀도지단백을 측정하여 골수이식 후 시기별 변화를 관찰하고 여러 임상인자들에 따른 차이를 알아보았다. 결과:1. 공복혈당은 골수이식 수 첫4주 동안 상승하였고 이후 감소하였으나 이식 6개월 시점의 평균 공복혈당은 이식 전보다 유의하게 높게 관찰되었다. 혈중 총 콜레스테롤은 이식 후 1주에 최고치를 형성하였고 이후 기저수준으로 회복되었다가 이식 수 3,6개월에 다시 증가하여 기저치에 비해 유의하게 높았다. 혈중 중성지방은 이식 후 1개월까지 유의하게 증가하였고 이후 감소하여, 3,6개월에는 기저치와 유의한 차이가 관찰되지 않았다. 혈중 고밀도지단백은 이식 후 2,3주에 이식 전보다 유의하게 감소하였고 이후 이식 전 수준으로 회복되었다. 혈중 저밀도지단백은 총 콜레스테롤의 변화와 매우 유사하였다. 2. 골수이식 후 6개월 시점에서 공복 혈당이 126㎎/dL이상인 환자는 7명(16%)이었다. 이들 환자들과 공복혈당 126㎎/dL 미만의 환자 36명을 비교한 결과, 공복혈당이 126㎎/dL 이상인 환자군에서 스테로이드 평균 투여량이 많았고 고밀도지단백이 유의하게 낮았다. 3. 이식편대숙주질환이 발생한 환자는 그렇지 않은 환자보다 이식 후 1, 2, 3주 및 6개월의 총 콜레스테롤이 더 낮았고, 3개월의 공복혈당이 더 높았다. 혈연골수이식 환자군은 비혈연골수이식 환자에 비해 투여된 스테로이드 용량이 더 적음에도 불구하고 이식 후 1, 2, 3주 및 6개월의 총 콜레스테롤 수치가 더 높았다. 스테로이드 고용량 투여군(하루 평균 7.5㎎기준)은 저용량군보다 이식 후 3개월 시점의 공복혈당이 더 높았으나 나머지 시점의 혈당, 혈중 지질농도에 있어서는 유의한 차이가 관찰되지 않았다. 결론:골수이식 후 초기시기에 주로 당 대사 및 지질대사이상이 관찰되며 이는 면역억제제 투여와 관련이 있음을 알 수 있었다. 면역억제제가 고용량 투여되는 합병증 발생 시 이들 대사이상에 관심을 기울여 대처해야 할 것이다. Background: In bone marrow transplantation(BMT), recipients are usually younger and immunosuppressants are open used in shorter period than in solid organ transplantation. Therefore, there might be a difference in glucose and lipid metabolism between BMT and solid organ transplantation. However, the serial changes of metabolic parameters following BMT have not been studied. Therefore, the aim of this study is to investigate the serial changes of blood glucose, lipids and the putative factors that are related with these changes after BMT. Methods: We have prospectively investigated 43 patients who underwent allogeneic BMT. Fasting plasma glucose(FPG), total cholesterol, triglyceride and high-density lipoprotein(HDL) were measured before BMT, and at 1, 2, 3, 4, 12 weeks and 6 months after BMT. The serial changes of these metabolic parameters according to clinical factors including type of BMT, mean daily steroid dosage, and occurrence of graft versus host disease (GVHD) were examined. Results: 1. Mean FPG level increased during 4 weeks after BMT and remained above basal value at post-transplant 6 months. Total Cholesterol level was increased during initial 4 weeks after BMT and was above basal value at post-BMT of 3 and 6 months. Triglyceride level was progressively increased during initial 4 weeks after BMT, but returned to basal value there after. HDL-cholesterol level was significantly decreased during initial 4 weeks after BMT, but returned to basal value there after. 2. Patients with FPG above 126 mg/dL and the other patients, the former received larger amounts of daily steroid and had lower HDL-cholesterol level. 3. The changes of metabolic parameters were different according to type of BMT, steroid dose, and occurrence of GVHD. Conclusion: Although there was increase of FPG, TC, TG and decrease of HDL-C during initial 4 weeks after BMT, these metabolic changes recovered slowly thereafter. Immunosuppressants are thought to be associated with these changes. Further observation will be needed for the long-term effect of BMT on metabolic changes(J Kor Diabetes Asso 24:689~698, 2000).

Hydrogen Behavior in Ti-Added Reduced Activation Ferritic-Martensitic Steels

Kang‑Mook Ryu,Dae Geon Lee,Joonoh Moon,Chang‑Hoon Lee,Tae‑Ho Lee,Jae Sang Lee,Dong‑Woo Suh 대한금속·재료학회 2021 METALS AND MATERIALS International Vol.27 No.3

Hydrogen behavior and corresponding mechanical degradation were examined in TaTi-RAFM and EUROFER97 steels. Increased Ta content with Ti addition decelerates the hydrogen diffusion but increases the solubility in the lattice. It ismainly led by the higher fraction of Ta-rich MC carbides and dislocation density in TaTi-RAFM steel. Overall activationenergy of hydrogen trapping of investigated steels is evaluated to be 25.3 ~ 25.6 kJ/mol in the tempered condition. The activationenergy increases to nearly 30 kJ/mol when the steels are re-austenitized and quenched. Higher activation energy withincreased dislocation density indicates that the dislocation provides for trap site with higher activation energy than Ta-richMC carbide. Mechanical degradation by hydrogen with respect to the yield strength, tensile strength and uniform elongationcould not be observed in all investigated steels. The presence of hydrogen only has influence on the loss of post-uniformelongation. For a given charging time, the loss of post-uniform elongation is more remarkable in TaTi-RAFM steel due tothe larger hydrogen uptake.

Functional Properties of Permeate Fractions Obtained from Bastard Halibut Roe Extracts by Ultrafiltration and It’s Biological Activities

Gyoon-Woo Lee1,In Seong Yoon,Su Gwang Lee,Jung-Suck Lee,Young-Mi Kang,Jin-Soo Kim,Min Soo Heu 한국수산해양기술학회(구 한국어업기술학회) 2016 한국수산해양기술학회 학술발표대회 Vol.2016 No.10

교사들의 공통과학 실험 · 실습 선호도 조사 분석

정원우,이윤종,강용희,윤일희,이우붕,손종경,김중욱,강동진,권용주 慶北大學校 師範大學 科學敎育硏究所 1999 科學敎育硏究誌 Vol.23 No.-

The purpose of this study is to investigate the status of the experimental and practical education in high school general science. The present status and reasonable management of the experimental and practical education in high school general science were evaluated by the questionaires. To do this, 146 science teachers in Korea are administered questionaires. The frequency of the experimental and practical items in the seven kind of general science text books were investigated. The problems and the reasonable management for experimental and practical education were proposed in this paper.

톨루엔 노출 근로자에서 유전자적 요인, 생활습관 및 식이가 요중 마뇨산 배설에 미치는 영향

임현우,박정일,노영만,이강숙,이정민,이원철,이세훈,정치경 大韓産業醫學會 2000 대한직업환경의학회지 Vol.12 No.3

목 적 : 본 연구는 생물학적 지표 특성 연구를 위한 단면조사 연구로서 톨루엔 노출과 톨루엔의 생물학적 모니터링으로 이용되는 요중 마뇨산 농도간의 양-반응 관계에서 효과 변경인자로서 작용하는 유전자 ALDH2, CYPIAI, CYP2El의 다양성 분포를 조사하고, 이들 유전자가 요중 마뇨산 배설 농도에 미치는 영향을 알아보고자 하였다. 방 법 : 연구대상자는 경인지역에 위치한 22개의 사업체에서 페인트 제조 72명, 제조업에서 도장작업 50명, 인쇄업 12명, 접착작업 12명, 벽지의 코팅작업 14명등 160명의 근로자이었다. 성, 연령, 유기용제 작업장 근무경력, 흡연습관, 음주습관, 검사일 이전 밤에 음주 여부, 시료 채취전 6시간 이내에 섭취한 식품조사, 측정일 개인보호구의 착용 여부에 대하여 설문조사를 시행하였다. 톨루엔에 대한 개인노출량은 passive air sampler로 측정하였고, 요중 마뇨산은 요중 크레아틴으로 보정하여 측정하였다. 또한 aldehyde dehydrogenase 2 (ALDH2) , cytochrome P45O IAI(CYPIAI), 그리고 cytochrome P45O 2El(CYPfEl)의 유전적 다양성은 혈액으로부터 백혈구의 DNA를 추출하여 제한 효소 절단 길이 다양성 (restiction fragment length polymorphism, RFLP)법으로 검사하여 다음의 결과를 얻었다. 결 과 : 연구대상자의 요중 마뇨산 농도의 기하평균은 0.44g/g creatinine, 기하표준편차 2.80이었다. 톨루엔 노출 농도, 개인 보호구 착용여부, 안식향산이 함유된 식품의 섭취여부중 요중 마뇨산 배설농도에 영향을 미치는 인자는 톨루엔 노출 농도뿐이었다. ALDH2, CYPIAI, CYPfEl, 연령, 흡연, 근무기간에서 회귀계수간에 차이를 보이는 경향이 있었다. 요중 마뇨산 농도에 대한 다중회귀분석에서 톨루엔, ALDH2, CYPIAI, CYP2El유전자형의 회귀계수가 통계적으로 유의하였다. 결 론 : 톨루엔 노출로 인한 요중 마뇨산 배설 농도는 ALDH2, CYPIAI, CYP2El유전자 다양성에 의해 영향을 받기 때문에, 유전자형의 대사능의 차이를 고려하여 마뇨산 기준 농도를 찾는 연구가 이루어져야 하겠다. Objectives The purpose was to investigate the distributions and the effects of genetic polymorphism of aldehyde dehydrogenase 2(ALDH2), cytochrome P45O IAI (CYPIAI), and cytochrome P45O 2El (CYPfEl) on the toluene metabolism. Methods : The subacts consisted of 160 workers who were exposed to toluene in different industries such as paint manufacturing, painting on steel and wood products, printing, bonding, and coating. The exposed toluene level was monitored by passive air sam paler, and the questionnaire variables were age, sex, smoking, drinking, previous night's drinking, use of personal protectlve equipment, work duration, and taking benzoic acid containing food. The urinary hippurric acid collected in the end of shift was corrected by urinary creatinine concentration. The genotypes of ALDH2, CYPIAI, and CYP2El were investigated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods with DNA extracted from venous blood. Results'The geometric mean and the geometric standard deviation of urinary hippuric acid concentration were 0.44 g/g creatinine and 2.80. The urinary hippuric acid concentration was significantly related to personal exposed toluene level among personal exposed toluene level, use of personal protective equipment, and benzoic acid containing food diet. The slope differences of the regression for ALDH2, CYPIAI, and CYP2E1 genetic polymorphism, age, smoking, and work duration tended to be significant. In multiple regression analysis, the regression coefficient of toluene, ALDH2, 7YPIAl, CYP2E1 genetic polymorphism were significant. Conclusions : From the above results, urinary hippuric acid level after toluene exposure was significantly affected by the genetic polymorphism of ALDH2, CYPIAI, CYPfEl. It is needed further investigation of the urinary hippuric acid level considering the effect of genetic polymorphism.

Erratum to: Intracellular Substrates of a Heme-Containing Ascorbate Oxidase in Pleurotus ostreatus

Seung-Rock Lee,Woo-Jeong Joo,Yong-Un Baek,Youn-Kyong Lee,Seong-Woon Yu,Yeon-Ran Kim,Kee-Oh Chay,Seung-Hyun Cho,Sa-Ouk Kang 한국미생물학회 2009 The journal of microbiology Vol.47 No.6

In the online version of the article the name of the second corresponding author is misspelled. The correct spelling is Sa-Ouk Kang. The online version of the original article can be found under doi: 10.1007/s12275-008-0307-8

벼, 콩 및 채소류에 대한 Mn-54, Co-60, Zn-65, Cs-137의 토양-작물체간 전이계수

박찬걸,조용우,최용호,김국찬,이창우,이강석,이정호 대한방사선 방어학회 1991 방사선방어학회지 Vol.16 No.2

벼, 콩, 상치, 당근, 호박의 가식부위에 대하여 몇가지 토양에 있어서 토양-작물체간 Mn-54, Co-60, Zn-65, Cs-137의 전이계수를 포트 재배에 의한 방사성 추적자 흡수실험을 통하여 조사하였다. 핵종간 전이계수는 거의 모든 경우 Zn-65>Mn-54>Cs-137>Co-60의 순이었다. 콩이 벼보다 전반적으로 한 자리 정도 높은 값을 보였고 채소류의 경우에는 대체로 상치에서 가장 높고 호박에서 가장 낮은 값을 보였다. 강산성 토양에서는 약산성 토양에서보다 전이계수가 훨씬 높았다. 본 조사결과에 입각하여 한국인의 섭식경로 피폭선량 평가에 이용하기 위한 각 핵종의 전이계수치가 작물별로 제안되었다. Soil-to plant transfer coefficients of Mn-54, Co-60, Zn-65 and Cs-137 were estimated for the edible parts of the rice, soybean, lettuce, carrot, and squash grown in different soils by radiotracer uptake experiments using pot cultures. The transfer coefficients of radionuclides were n the order of Zn-65>Mn-54>Cs-137>Co-60 in most of the cases studied. The coefficients for soybean were roughly and order of magnitude higher than those for rice. Among vegetables, lettuce mostly showed the highest value and squash, the lowest. In the strongly acidic soils. From the data obtained, crop-specific transfer coefficients of the four nuclides were proposed for the use in Korean food-radiation dose assessment.

하악 제3대구치의 존재여부 및 매복양상이 하악 우각부 골절과 과두 골절의 발생에 미치는 영향

이영주(Young-Joo Lee),송윤정(Yun-Jung Song),홍순민(Soon-Min Hong),채상식(Sang-Sik Chae),강현우(Hyeon-Woo Kang),최동주(Dong-Ju Choi),박준우(Jun-Woo Park) 대한치과의사협회 2012 대한치과의사협회지 Vol.50 No.9

Purpose : This study evaluated the impact of the presence and aspect of mandibular third molars to the mandible angle fracture or condyle fractures in Korean. Materials and Methods : A retrospective study was designed for patients attending the division of Oral and Maxillofacial Surgery, Kang-dong sacred heart hospital for treatment of mandibular fracture from January 2006 to September 2010. The primary variable was the presence of mandibular third molar and the secondary variable was the aspects of third molar impaction. Mandibular third molars were classified by the impaction depth and the available space as Pell & Gregory system. Outcome variables were the presence of mandibular angle fracture or condyle fracture. Also the source of trauma, age, sex were studied. Hospital charts, radiographs were used for study. Statistic analysis was done with descriptive statistics, the X2-test, linear-bylinear association. P value under 0.05 was considered significant statistically. Results : The number of involved patients was 86. The ratio of male to female patients was about 9:1 for angle fracture and 7:3 for condyle fracture. The most common source of trauma was assault for angle fracture and fall down for condyle fracture. The presence of mandibular third molar increased frequency of angle fracture and decreased condyle fracture with larger impaction depth. But available space of mandibular third molar did not show high association with angle or condyle fractures. Conclusion : Preventive extraction of mandibular third molar is recommended for patients with high risk of angle fracture. Male patients at their third decade or martial artists, police officer could be the case. But it is not recommended for patients with low risk of angle fracture and high risk of condyle fracture relatively. Elder female patients without any symptom on their third molar could be the case.